Characterization of Tetrahydrolipstatin and Stereoderivatives on the Inhibition of Essential Mycobacterium tuberculosis Lipid Esterases.

ABSTRACT: Tetrahydrolipstatin (THL) is a covalent inhibitor of many serine esterases. In mycobacteria, THL has been found to covalently react with 261 lipid esterases upon treatment of Mycobacterium bovis cell lysate. However, the covalent adduct is considered unstable in some cases because of the hydrolysis of the enzyme-linked THL adduct resulting in catalytic turnover. In this study, a library of THL stereoderivatives was tested against three essential Mycobacterium tuberculosis lipid esterases of interest for drug development to assess how the stereochemistry of THL affects respective enzyme inhibition and allows for cross enzyme inhibition. The mycolyltransferase Antigen 85C (Ag85C) was found to be stereospecific with regard to THL; covalent inhibition occurs within minutes and was previously s

SUBMITTER: Goins CM 

PROVIDER: S-EPMC6128263 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature